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Implications of Using a Highly Sensitive Serological Test as a Screening Modality for the Diagnosis of Syphilis

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Abstract

Traditionally, syphilis has been diagnosed by clinical findings, supported by serological evidence of the disease. Newer treponemal tests such as Treponema pallidum-specific captia syphilis immunoglobulin G assay and the immune-capture immunoassay are more sensitive and specific than the conventional tests (rapid plasma reagin and VDRL). This raises the concern that those facilities that have not adopted these newer tests may be underdiagnosing cases of syphilis.

To the Editor:

Traditionally, syphilis has been diagnosed by clinical findings, supported by serological evidence of the disease. A nontreponemal antibody test such as rapid plasma reagin (RPR) or VDRL is used as the screening test and, if positive, confirmed by specific treponemal tests, such as fluorescent treponemal antibody test or Treponema pallidum hemagglutination assay. The high rates of false-negative nontreponemal antibody tests in primary and late latent stages of syphilis are well known. In recent years, newer treponemal tests with a significantly higher sensitivity and specificity than the conventional tests have been introduced.1 Some of these tests have been recommended to be used as the screening tests.2 However, Centers for Disease Control and Prevention has not revised the recommendation of performing a nontreponemal antibody test for screening.3

These newer treponemal antibody tests for syphilis are reported to be more sensitive and specific than the conventional screening nontreponemal tests. These tests include the enzyme immunoassays: T. pallidum-specific captia syphilis immunoglobulin (Ig) G assay, Centocor, and the immune-capture immunoassay that uses 3 recombinant T. pallidum antigens (ICE Syphilis; Murex Diagnostics).1,4 One year ago, our institution adopted the policy of performing the T. pallidum-specific captia syphilis IgG assay as the screening test and, if positive, RPR titers to measure the disease activity. Since then, we have noticed patients with a positive IgG but a negative RPR. Approximately 10 to 15 of our approximately 275 patients with human immunodeficiency virus who were previously RPR negative had a positive IgG and a negative RPR on routine annual syphilis screening. None of these patients had physical signs of primary or secondary syphilis, and an IgM test was not done. We did not offer additional treatment to those patients who had a history of treatment for syphilis. The patients without such treatment history have been treated for late latent syphilis. Patients with symptoms and signs suggestive of neurosyphilis underwent lumbar puncture-all of which were normal.

A review of literature suggests that some of the newer tests have nearly 100% sensitivity and specificity, even in the primary and latent stages of syphilis.1 This suggests that those facilities which have not adopted these newer tests may be underdiagnosing syphilis. If a highly sensitive and specific IgG test is adopted as the screening test, then there is a need for revision of guidelines to bring uniformity to screening.

When a nontreponemal test is used for screening and found to be negative, no additional workup is done for asymptomatic patients. Lumbar puncture is recommended to exclude neurosyphilis in those asymptomatic patients with human immunodeficiency virus and with no prior history of treatment and positive nontreponemal and treponemal tests, assuming that they have late latent syphilis or syphilis of unknown duration.3 Should we follow the same recommendation and offer lumbar puncture to a patient who has a positive specific treponemal IgG test but a negative nontreponemal serology?